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| 1 | Upgrading Pathways of Intelligent Manufacturing in China:Transitioning across Technological Paradigms显示文摘Intelligent technologies are leading to the next wave of industrial revolution in manufacturing.In developed economies,firms are embracing these advanced technologies following a sequential upgrading strategy-from digital manufacturing to smart manufacturing(digital-networked),and then to newgeneration intelligent manufacturing paradigms.However,Chinese firms face a different scenario.On the one hand,they have diverse technological bases that vary from low-end electrified machinery to leading-edge digital-network technologies;thus,they may not follow an identical upgrading pathway.On the other hand,Chinese firms aim to rapidly catch up and transition from technology followers to probable frontrunners;thus,the turbulences in the transitioning phase may trigger a precious opportunity for leapfrogging,if Chinese manufacturers can swiftly acquire domain expertise through the adoption of intelligent manufacturing technologies.This study addresses the following question by conducting multiple case studies:Can Chinese firms upgrade intelligent manufacturing through different pathways than the sequential one followed in developed economies?The data sources include semistructured interviews and archival data.This study finds that Chinese manufacturing firms have a variety of pathways to transition across the three technological paradigms of intelligent manufacturing in nonconsecutive ways.This finding implies that Chinese firms may strategize their own upgrading pathways toward intelligent manufacturing according to their capabilities and industrial specifics;furthermore,this finding can be extended to other catching-up economies.This paper provides a strategic roadmap as an explanatory guide to manufacturing firms,policymakers,and investors. | Yuan Zhou Jiyuan Zang Zhongzhen Miao Tim Minshall | 2019 | Engineering2019，5，4： | 42 |
| 2 | Mechanism underlying treatment of ischemic stroke using acupuncture:transmission and regulation显示文摘The inflammatory response after cerebral ischemia/reperfusion is an important cause of neurological damage and repair.After cerebral ischemia/reperfusion,microglia are activated,and a large number of circulating inflammatory cells infiltrate the affected area.This leads to the secretion of inflammatory mediators and an inflammatory cascade that eventually causes secondary brain damage,including neuron necrosis,blood-brain barrier destruction,cerebral edema,and an oxidative stress response.Activation of inflammatory signaling pathways plays a key role in the pathological process of ischemic stroke.Increasing evidence suggests that acupuncture can reduce the inflammatory response after cerebral ischemia/reperfusion and promote repair of the injured nervous system.Acupuncture can not only inhibit the activation and infiltration of inflammatory cells,but can also regulate the expression of inflammation-related cytokines,balance the effects of pro-inflammatory and anti-inflammatory factors,and interfere with inflammatory signaling pathways.Therefore,it is important to study the transmission and regulatory mechanism of inflammatory signaling pathways after acupuncture treatment for cerebral ischemia/reperfusion injury to provide a theoretical basis for clinical treatment of this type of injury using acupuncture.Our review summarizes the overall conditions of inflammatory cells,mediators,and pathways after cerebral ischemia/reperfusion,and discusses the possible synergistic intervention of acupuncture in the inflammatory signaling pathway network to provide a foundation to explore the multiple molecular mechanisms by which acupuncture promotes nerve function restoration. | Bing-Qian Cao Feng Tan Jie Zhan Peng-Hui Lai | 2021 | Neural Regeneration Research2021，16，5： | 43 |
| 3 | Electroacupuncture improves learning and memory functions in a rat cerebral ischemia/reperfusion injury model through PI3K/Akt signaling pathway activation显示文摘Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia,but the underlying mechanism has not yet been fully elucidated.Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment,and the phosphoinositide 3-kinase(PI3K)/Akt signaling pathway plays an important role in autophagy regulation.To investigate the role played by the PI3K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models,we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method.Starting at 2 hours after modeling,electroacupuncture was delivered at the Shenting(GV24)and Baihui(GV20)acupoints,with a dilatational wave(1-20 Hz frequency,2 mA intensity,6 V peak voltage),for 30 minutes/day over 8 consecutive days.Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury,increased the mRNA expression levels of the PI3K/Akt signaling pathwayrelated factors Beclin-1,mammalian target of rapamycin(mTOR),and PI3K,increased the protein expression levels of phosphorylated Akt,Beclin-1,PI3K,and mTOR in the ischemic cerebral cortex,and simultaneously reduced p53 mRNA and protein expression levels.In the Morris water maze test,the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.In the spatial probe test,the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.Electroacupuncture stimulation applied to the Shenting(GV24)and Baihui(GV20)acupoints activated the PI3K/Akt signaling pathway and improved rat learning and memory impairment.This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,China(approval No.8150150901)on March 10,2016. | Hui-Ling Wang Fei-Lai Liu Rui-Qing Li Ming-Yue Wan Jie-Ying Li Jing Shi Ming-Li Wu Jun-Hua Chen Wei-Juan Sun Hong-Xia Feng Wei Zhao Jin Huang Ren-Chao Liu Wen-Xue Hao Xiao-Dong Feng | 2021 | Neural Regeneration Research2021，16，6： | 48 |
| 4 | Mechanism of delayed encephalopathy after acute carbon monoxide poisoning显示文摘Many hypotheses exist regarding the mechanism underlying delayed encephalopathy after acute carbon monoxide poisoning(DEACMP),including the inflammation and immune-mediated damage hypothesis and the cellular apoptosis and direct neuronal toxicity hypothesis;however,no existing hypothesis provides a satisfactory explanation for the complex clinical processes observed in DEACMP.Leucine-rich repeat and immunoglobulin-like domain-containing protein-1(LINGO-1)activates the Ras homolog gene family member A(Rho A)/Rho-associated coiled-coil containing protein kinase 2(ROCK2)signaling pathway,which negatively regulates oligodendrocyte myelination,axonal growth,and neuronal survival,causing myelin damage and participating in the pathophysiological processes associated with many central nervous system diseases.However,whether LINGO-1 is involved in DEACMP remains unclear.A DEACMP model was established in rats by allowing them to inhale 1000 ppm carbon monoxide gas for 40 minutes,followed by 3000 ppm carbon monoxide gas for an additional 20 minutes.The results showed that compared with control rats,DEACMP rats showed significantly increased water maze latency and increased protein and m RNA expression levels of LINGO-1,Rho A,and ROCK2 in the brain.Compared with normal rats,significant increases in injured neurons in the hippocampus and myelin sheath damage in the lateral geniculate body were observed in DEACMP rats.From days 1 to 21 after DEACMP,the intraperitoneal injection of retinoic acid(10 mg/kg),which can inhibit LINGO-1 expression,was able to improve the above changes observed in the DEACMP model.Therefore,the overexpression of LINGO-1 appeared to increase following carbon monoxide poisoning,activating the Rho A/ROCK2 signaling pathway,which may be an important pathophysiological mechanism underlying DEACMP.This study was reviewed and approved by the Medical Ethics Committee of Xiangya Hospital of Central South Hospital(approval No.201612684)on December 26,2016. | Yan-Qing Huang Zheng-Rong Peng Fang-Ling Huang A-Li Yang | 2020 | Neural Regeneration Research2020，15，12： | 35 |
| 5 | Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injury显示文摘Apelin-13 is a novel endogenous ligand for an angiotensin-like orphan G-protein coupled receptor,and it may be neuroprotective against cerebral ischemia injury.However,the precise mechanisms of the effects of apelin-13 remain to be elucidated.To investigate the effects of apelin-13 on apoptosis and autophagy in models of cerebral ischemia/reperfusion injury,a rat model was established by middle cerebral artery occlusion.Apelin-13(50μg/kg)was injected into the right ventricle as a treatment.In addition,an SH-SY5Y cell model was established by oxygen-glucose deprivation/reperfusion,with cells first cultured in sugar-free medium with 95%N2 and 5%CO2 for 4 hours and then cultured in a normal environment with sugar-containing medium for 5 hours.This SH-SY5Y cell model was treated with 10-7 M apelin-13 for 5 hours.Results showed that apelin-13 protected against cerebral ischemia/reperfusion injury.Apelin-13 treatment alleviated neuronal apoptosis by increasing the ratio of Bcl-2/Bax and significantly decreasing cleaved caspase-3 expression.In addition,apelin-13 significantly inhibited excessive autophagy by regulating the expression of LC3B,p62,and Beclin1.Furthermore,the expression of Bcl-2 and the phosphatidylinositol-3-kinase(PI3K)/Akt/mammalian target of rapamycin(mTOR)pathway was markedly increased.Both LY294002(20μM)and rapamycin(500 nM),which are inhibitors of the PI3K/Akt/mTOR pathway,significantly attenuated the inhibition of autophagy and apoptosis caused by apelin-13.In conclusion,the findings of the present study suggest that Bcl-2 upregulation and mTOR signaling pathway activation lead to the inhibition of apoptosis and excessive autophagy.These effects are involved in apelin-13-induced neuroprotection against cerebral ischemia/reperfusion injury,both in vivo and in vitro.The study was approved by the Animal Ethical and Welfare Committee of Jining Medical University,China(approval No.2018-JS-001)in February 2018. | Zi-Qi Shao Shan-Shan Dou Jun-Ge Zhu Hui-Qing Wang Chun-Mei Wang Bao-Hua Cheng Bo Bai | 2021 | Neural Regeneration Research2021，16，6： | 35 |
| 6 | Epithelial-mesenchymal transition- activating transcription factors- multifunctional regulators in cancer显示文摘The process of epithelial to mesenchymal transition(EMT), first noted during embryogenesis, has also been reported in tumor formation and leads to the development of metastatic growth. It is a naturally occurring process that drives the transformation of adhesive,non-mobile epithelial like cells into mobile cells with a mesenchymal phenotype that have ability to migrate to distant anatomical sites. Activating complex network of embryonic signaling pathways, including Wnt, Notch,hedgehog and transforming growth factor-β pathways,lead to the upregulation of EMT activating transcription factors, crucial for normal tissue development and maintenance. However, deregulation of tightly regulated pathways affecting the process of EMT has been recently investigated in various human cancers. Given the critical role of EMT in metastatic tumor formation,better understanding of the mechanistic regulation provides new opportunities for the development of potential therapeutic targets of clinical importance. | Minal Garg | 2013 | World Journal of Stem Cells2013，5，4： | 26 |
| 7 | Molecular regulation of vasculogenic mimicry in tumors and potential tumor-target therapy显示文摘'Vasculogenic mimicry(VM)',is a term that describes the unique ability of highly aggressive tumor cells to express a multipotent,stem cell-like phenotype,and form a pattern of vasculogenic-like networks in threedimensional culture.As an angiogenesis-independent pathway,VM and/or periodic acid-schiff-positive patterns are associated with poor prognosis in tumor patients.Moreover,VM is resistant to angiogenesis inhibitors.Here,we will review the advances in research on biochemical and molecular signaling pathways of VM in tumors and on potential anti-VM therapy strategy. | Yue-Zu Fan Wei Sun | 2010 | World Journal of Gastrointestinal Surgery2010，2，4： | 19 |
| 8 | Dissecting the molecular pathophysiology of drug-induced liver injury显示文摘Drug-induced liver injury(DILI) has become a major topic in the field of Hepatology and Gastroenterology. DILI can be clinically divided into three phenotypes: hepatocytic, cholestatic and mixed. Although the clinical manifestations of DILI are variable and the pathogenesis complicated, recent insights using improved preclinical models, have allowed a better understanding of the mechanisms that trigger liver damage. In this review, we will discuss the pathophysiological mechanisms underlying DILI. The toxicity of the drug eventually induces hepatocellular damage through multiple molecular pathways, including direct hepatic toxicity and innate and adaptive immune responses. Drugs or their metabolites, such as the common analgesic, acetaminophen, can cause direct hepatic toxicity through accumulation of reactive oxygen species and mitochondrial dysfunction. The innate and adaptive immune responses play also a very important role in the occurrence of idiosyncratic DILI. Furthermore, we examine common forms of hepatocyte death and their association with the activation of specific signaling pathways. | Hui Ye Leonard J Nelson Manuel Gómez del Moral Eduardo Martínez-Naves Francisco Javier Cubero | 2018 | World Journal of Gastroenterology2018，24，13： | 19 |
| 9 | A survey of web resources and tools for the study of TCM network pharmacology显示文摘Background: Traditional Chinese medicine (TCM) treats diseases in a holistic manner, while TCM formulae are multi-component, multi-target agents at the molecular level. Thus there are many parallels between the key ideas of TCM pharmacology and network pharmacology. These years, TCM network pharmacology has developed as an interdisciplinary of TCM science and network pharmacology, which studies the mechanism of TCM at the molecular level and in the context of biological networks. It provides a new research paradigm that can use modern biomedical science to interpret the mechanism of TCM, which is promising to accelerate the modernization and internationalization of TCM? Results: In this paper we introduce state-of-the-art free data sources, web servers and softwares that can be used in the TCM network pharmacology, including databases of TCM, drug targets and diseases, web servers for the prediction of drug targets, and tools for network and functional analysis. Conclusions: This review could help experimental pharmacologists make better use of the existing data and methods in their study of TCM. | Jing Zhao Jian Yang Saisai Tian Weidong Zhang | 2019 | Frontiers of Electrical and Electronic Engineering in China2019，7，1： | 17 |
| 10 | Enriched environment boosts the post-stroke recovery of neurological function by promoting autophagy显示文摘Autophagy is crucial for maintaining cellular homeostasis,and can be activated after ischemic stroke.It also participates in nerve injury and repair.The purpose of this study was to investigate whether an enriched environment has neuroprotective effects through affecting autophagy.A Sprague-Dawley rat model of transient ischemic stroke was prepared by occlusion of the middle cerebral artery followed by reperfusion.One week after surgery,these rats were raised in either a standard environment or an enriched environment for 4 successive weeks.The enriched environment increased Beclin-1 expression and the LC3-II/LC3-I ratio in the autophagy/lysosomal pathway in the penumbra of middle cerebral artery-occluded rats.Enriched environment-induced elevations in autophagic activity were mainly observed in neurons.Enriched environment treatment also promoted the fusion of autophagosomes with lysosomes,enhanced the lysosomal activities of lysosomal-associated membrane protein 1,cathepsin B,and cathepsin D,and reduced the expression of ubiquitin and p62.After 4 weeks of enriched environment treatment,neurological deficits and neuronal death caused by middle cerebral artery occlusion/reperfusion were significantly alleviated,and infarct volume was significantly reduced.These findings suggest that neuronal autophagy is likely the neuroprotective mechanism by which an enriched environment promotes recovery from ischemic stroke.This study was approved by the Animal Ethics Committee of the Kunming University of Science and Technology,China(approval No.5301002013855)on March 1,2019. | Yi-Hao Deng Ling-Ling Dong Yong-Jie Zhang Xiao-Ming Zhao Hong-Yun He | 2021 | Neural Regeneration Research2021，16，5： | 17 |
| 11 | Endoplasmic reticulum stress-mediated pathways to both apoptosis and autophagy: Significance for melanoma treatment显示文摘Melanoma is the most aggressive form of skin cancer.Disrupted intracellular signaling pathways are responsible for melanoma's extraordinary resistance to current chemotherapeutic modalities. The pathophysiologic basis for resistance to both chemo- and radiation therapy is rooted in altered genetic and epigenetic mechanisms that, in turn, result in the impairing of cell death machinery and/or excessive activation of cell growth and survival-dependent pathways. Although most current melanoma therapies target mitochondrial dysregulation,there is increasing evidence that endoplasmic reticulum(ER) stress-associated pathways play a role in the potentiation,initiation and maintenance of cell death machinery and autophagy. This review focuses on the reliability of ER-associated pathways as therapeutic targets for melanoma treatment. | Mohamed Hassan Denis Selimovic Matthias Hannig Youssef Haikel Robert T Brodell Mossaad Megahed | 2015 | World Journal of Experimental Medicine2015，5，4： | 15 |
| 12 | Microbial Degradation of Organophosphate Pesticides: A Review显示文摘Pesticides have become an inevitable part of the modern environment as they are widely used in agriculture,household,and public health sectors and,hence,are extensively distributed throughout most ecosystems.Currently,organophosphate pesticides are the most commercially favored group of pesticides,with large application areas all over the world.Depending on their fate,these organophosphorus compounds may become bioavailable for microbial degradation.Environmental microbes,such as Aspergillus,Pseudomonas,Chlorella,and Arthrobacter,are capable of coupling a variety of physical and biochemical mechanisms for the degradation of organophosphate pesticides,including adsorption,hydrolysis of P–O alkyl and aryl bonds,photodegradation,and enzymatic mineralization.Enzymes,such as esterase,diisopropyl fluorophosphatase,phosphotriesterase,somanase,parathion hydrolase,and paraoxonase,have been isolated from microbes to study and understand the catabolic pathways involved in the biotransformation of these xenobiotic compounds.This review highlights various aspects of biodegradation of organophosphate pesticides along with biological and molecular characterization of some organophosphate pesticide-degrading bacteria. | Shardendu KUMAR Garima KAUSHIK Mohd Ashraf DAR Surendra NIMESH Ulrico Javier LOPEZ-CHUKEN Juan Francisco VILLARREAL-CHIU | 2018 | Pedosphere2018，28，2： | 12 |
| 13 | Targeting cancer stem cell pathways for cancer therapy显示文摘Since cancer stem cells(CSCs)were first identified in leukemia in 1994,they have been considered promising therapeutic targets for cancer therapy.These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies,such as recurrence,metastasis,heterogeneity,multidrug resistance,and radiation resistance.The biological activities of CSCs are regulated by several pluripotent transcription factors,such as OCT4,Sox2,Nanog,KLF4,and MYC.In addition,many intracellular signaling pathways,such as Wnt,NF-κB(nuclear factor-κB),Notch,Hedgehog,JAK-STAT(Janus kinase/signal transducers and activators of transcription),PI3K/AKT/mTOR(phosphoinositide 3-kinase/AKT/mammalian target of rapamycin),TGF(transforming growth factor)/SMAD,and PPAR(peroxisome proliferator-activated receptor),as well as extracellular factors,such as vascular niches,hypoxia,tumor-associated macrophages,cancer-associated fibroblasts,cancer-associated mesenchymal stem cells,extracellular matrix,and exosomes,have been shown to be very important regulators of CSCs.Molecules,vaccines,antibodies,and CAR-T(chimeric antigen receptor T cell)cells have been developed to specifically target CSCs,and some of these factors are already undergoing clinical trials.This review summarizes the characterization and identification of CSCs,depicts major factors and pathways that regulate CSC development,and discusses potential targeted therapy for CSCs. | Liqun Yang Pengfei Shi Gaichao Zhao Jie Xu Wen Peng Jiayi Zhang Guanghui Zhang Xiaowen Wang Zhen Dong Fei Chen Hongjuan Cui | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 12 |
| 14 | Ursolic acid: An overview on its cytotoxic activities against breast and colorectal cancer cells显示文摘Ursolic acid(UA) is a pentacyclic triterpene of the ursane type. As a common chemical constituent among species of the family Lamiaceae, UA possesses a broad spectrum of pharmacological properties. This overview focuses on the anticancer properties of UA against breast cancer(BC) and colorectal cancer(CRC)that are most common among women and men, respectively. In vitro studies have shown that UA inhibited the growth of BC and CRC cell lines through various molecular targets and signaling pathways.There are several in vivo studies on the cytotoxic activity of UA against BC and CRC. UA also inhibits the growth of other types of cancer. Studies on structural modifications of UA have shown that the –OH groups at C3 and at C28 are critical factors influencing the cytotoxic activity of UA and its derivatives.Some needs for future research are suggested. Sources of information were from ScienceDirect, Google Scholar and PubMed. | Eric Wei Chiang Chan Chu Yong Soon Joash Ban Lee Tan Siu Kuin Wong Yew Woh Hui | 2019 | Journal of Integrative Medicine2019，17，3： | 11 |
| 15 | Inflammatory role of the acinar cells during acute pancreatitis显示文摘Pancreatic acinar cells are secretory cells whose main function is to synthesize, store and f inally release digestive enzymes into the duodenum. However, in response to noxious stimuli, acinar cells behave like real inflammatory cells because of their ability to activate signalling transduction pathways involved in the expression of inflammatory mediators. Mediated by the kinase cascade, activation of Nuclear factor-κB, Activating factor-1 and Signal transducers and activators of transcription transcription factors has been demonstrated in acinar cells, resulting in overexpression of inflammatory genes. In turn, kinase activity is down-regulated by protein phosphatases and the f inal balance between kinase and phosphatase activity will determine the capability of the acinar cells to produce inflammatory factors. The kinase/ phosphatase pair is a redox-sensitive system in which kinase activation overwhelms phosphatase activity under oxidant conditions. Thus, the oxidative stress developed within acinar cells at early stages of acute pancreatitis triggers the activation of signalling pathways involved in the up-regulation of cytokines, chemokines and adhesion molecules. In this way, acinar cells trigger the release of the f irst inflammatory signals which can mediate the activation and recruitment of circulating inflammatorycells into the injured pancreas. Accordingly, the role of acinar cells as promoters of the inflammatory response in acute pancreatitis may be considered. This concept leads to amplifying the focus from leukocyte to acinar cells themselves, to explain the local inflammation in early pancreatitis. | Isabel De Dios | 2010 | World Journal of Gastrointestinal Pharmacology and Therapeutics2010，1，1： | 11 |
| 16 | Dandelion polyphenols protect against acetaminophen-induced hepatotoxicity in mice via activation of the Nrf-2/HO-1 pathway and inhibition of the JNK signaling pathway显示文摘We investigated the liver protective activity of dandelion polyphenols(DP)against acetaminophen(APAP;Paracetamol)-induced hepatotoxicity.Mice were acclimated for 1 week and randomly divided into the following groups(n=9 per group):Control,APAP,APAP+DP(100 mg·kg^–1),APAP+DP(200 mg·kg^–1),and APAP+DP(400 mg·kg^–1)groups.Mice were pretreated with DP(100,200,and 400 mg·kg^–1)by oral gavage for 7 d before being treated with 350 mg·kg^–1 APAP for 24 h to induced hepatotoxicity.Severe liver injury was observed,and hepatotoxicity was analyzed after 24 h by evaluation of biochemical markers,protein expressions levels,and liver histopathology.Pretreatment with DP was able to restore serum liver characteristics(aspartate transaminase,AST;alanine aminotransferase,ALT;alkaline phosphatase,AKP),improve redox imbalance(superoxide dismutase,SOD;glutathione,GSH;malondialdehyde,MDA),and decrease inflammatory factors(tumor necrosis factor-α,TNF-α;interleukin-1β,IL-1β).Pretreatment with DP also significantly inhibited the expression levels of nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2).Furthermore,DP pretreatment could inhibit the apoptosis of liver cells caused by APAP through up-regulation of Bcl-2 and down-regulation of Bax and caspase-9 protein.DP also down-regulated p-JNK protein expression levels to inhibit APAP-induced mitochondrial oxidative stress and up-regulated the expression of Nrf-2 and its target gene HO-1.The histopathological staining demonstrated that DP pretreatment could inhibit APAP-induced hepatocyte infiltration,congestion,and necrosis.Our results demonstrate that DP pretreatment could protect against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway. | REN Yong-Shen ZHENG Yao DUAN Huan LEI Lei DENG Xin LIU Xin-Qiao MEI Zhi-Nan DENG Xu-Kun | 2020 | Chinese Journal of Natural Medicines2020，18，2： | 11 |
| 17 | Protective effects of extracts of Schisandra chinensis stems against acetaminophen-induced hepatotoxicity via regulation of MAPK and caspase-3 signaling pathways显示文摘The present study was designed to evaluate protective activity of an ethanol extract of the stems of Schisandra chinensis(SCE) and explore its possible molecular mechanisms on acetaminophen(APAP) induced hepatotoxicity in a mouse model. The results of HPLC analysis showed that the main components of SCE included schisandrol A, schisandrol B, deoxyschisandrin, schisan--drin B, and schisandrin C and their contents were 5.83, 7.11, 2.13, 4.86, 0.42 mg·g^(-1), respectively. SCE extract was given for 7 con--secutive days before a single hepatotoxic dose of APAP(250 mg·kg^(-1)) was injected to mice. Our results showed that SCE pretreatment ameliorated liver dysfunction and oxidative stress, which was evidenced by significant decreases in aspartate transaminase(AST), alanine aminotransferase(ALT), malondialdehyde(MDA) contents and elevations in reduced glutathione(GSH) and superoxide dismutase(SOD) levels. These findings were associated with the result that the SCE pretreatment significantly decreased expression levels of 4-hydroxynonenal(4-HNE) and 3-nitrotyrosine(3-NT). SCE also significantly decreased the expression levels of Bax, mitogen-activated protein kinase(MAPK), and cleaved caspase-3 by APAP exposure. Furthermore, supplementation with SCE suppressed the expression levels of inducible nitric oxide synthase(iNOS) and cyclooxygenase-2(COX-2), suggesting alleviation of inflammatory response. In summary, these findings from the present study clearly demonstrated that SCE exerted significant alleviation in APAP-induced oxidative stress, inflammation and apoptosis mainly via regulating MAPK and caspase-3 signaling pathways. | LI Yan-Zi Ma Zhi-Na SUN Yin-Shi REN Shen JIANG Shuang ZHANG Wei-Zhe WANG Zi LI Wei | 2018 | Chinese Journal of Natural Medicines2018，16，9： | 10 |
| 18 | Apoptotic pathways as a therapeutic target for colorectal cancer treatment显示文摘Colorectal cancer is the second leading cause of death from cancer among adults. The disease begins as a benign adenomatous polyp, which develops into an advanced adenoma with high-grade dysplasia and then progresses to an invasive cancer. Appropriate apoptotic signaling is fundamentally important to preserve a healthy balance between cell death and cell survival and in maintaining genome integrity. Evasion of apoptotic pathway has been established as a prominent hallmark of several cancers. During colorectal cancer development, the balance between the rates of cell growth and apoptosis that maintains intestinal epithelial cell homeostasis gets progressively disturbed. Evidences are increasingly available to support the hypothesis that failure of apoptosis may be an important factor in the evolution of colorectal cancer and its poor response to chemotherapy and radiation. The other reason for targeting apoptotic pathway in the treatment of cancer is based on the observation that this process is deregulated in cancer cells but not in normal cells. As a result, colorectal cancer therapies designed to stimulate apoptosis in target cells would play a critical role in controlling its development and progression. A better understanding of the apoptotic signaling pathways, and the mechanisms by which cancer cells evade apoptotic death might lead to effective therapeutic strategies to inhibit cancer cell proliferation with minimal toxicity and high responses to chemotherapy. In this review, we analyzed the current understanding and future promises of apoptotic pathways as a therapeutic target in colorectal cancer treatment. | Aman M Abraha Ezra B Ketema | 2016 | World Journal of Gastrointestinal Oncology2016，8，8： | 10 |
| 19 | Updates on the hepatocyte growth factor/c-Met axis in hepatocellular carcinoma and its therapeutic implications显示文摘Hepatocellular carcinoma(HCC) is the fifth most common cancer and is the second leading cause of cancer death. Since the diagnosis of HCC is difficult, in many cases patients with HCC are diagnosed advanced stage of development. Hepatocyte growth factor(HGF)/c-mesenchymal-epithelial transition receptor(c-Met) axis is a key signaling pathway in HCC, either via canonical or non-canonical pathways. Available treatments against HCC based upon HGF/c-Met inhibition can increase patient lifespan, but do not reach the expected therapeutic benefits. In HCC, c-Met monomers can bind other receptor monomers, activating several noncanonical signaling pathways, leading to increased cell proliferation, invasion, motility, and drug resistance. All of these processes are enhanced by the tumor microenvironment, with stromal cells contributing to boost tumor progression through oxidative stress, angiogenesis, lymphangiogenesis, inflammation, and fibrosis. Novel treatments against HCC are being explored to modulate other targets such as microR NAs, methyltransferases, and acetyltransferases, which are all involved in the regulation of gene expression in cancer. This review compiles basic knowledge regarding signaling pathways in HCC, and compounds already used or showing potential to be used in clinical trials. | Javier A García-Vilas Miguelángel Medina | 2018 | World Journal of Gastroenterology2018，24，33： | 10 |
| 20 | 肠的障碍: 分子的小径和修饰词显示文摘 The gastrointestinal tract is frequently challenged by pathogens/antigens contained in food and water and the intestinal epithelium must be capable of rapid regeneration in the event of tissue damage. Disruption of the intestinal barrier leads to a number of immune-mediated diseases, including inflammatory bowel disease, food allergy, and celiac disease. The intestinal mucosa is composed of different types of epithelial cells in specific barrier functions. Epithelial cells control surfaceassociated bacterial populations without disrupting the intestinal microflora that is crucial for host health. They are also capable of modulating mucosal immune system, and are thus essential in maintaining homeostasis in the gut. Thus, the regulation of intestinal epithelial homeostasis is crucial for the maintenance of the structure of the mucosa and the defensive barrier functions. Recent studies have demonstrated that multiple molecular pathways are involved in the regulation of intestinal epithelial cell polarity. These include the Wnt, Notch, Hippo, transforming growth factor-β(TGF-β)/bone morphogenetic protein(BMP) and Hedgehog pathways, most of which were identified in lower organisms where they play important roles during embryogenesis. These pathways are also used in adult organisms to regulate multiple self-renewing organs. Understanding the interactions between these molecular mechanisms and intestinal barrier function will therefore provide important insight into the pathogenesis of intestinal-based immune-mediated diseases. | Min Kyung Jeon Christina Klaus Elke Kaemmerer Nikolaus Gassler | 2013 | World Journal of Gastrointestinal Pathophysiology2013，4，4： | 10 |
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